Control of Endemic MRSA Current Evidence and Controversies

Control of Endemic MRSACurrent Evidence and

ControversiesGonzalo Bearman MD, MPH

Assistant Professor of MedicineAssociate Hospital Epidemiologist

Outline• SHEA Guidelines• What is the Quality of the Data?

– Limitations of epidemiologic study methods • Few randomized clinical trials• Multiple simultaneous interventions• Regression towards the mean

– Recent critical review of data on hospital MRSA control

• Cooper et al. Health Technology Assessment 2003; Vol. 7:No. 39

• Boyce et al. ICHE 2004. Vol 25. No.5 pgs 395-401

• Unintended consequences of contact isolation for infection control– JAMA. 2003;290:1899-1905

• Conclusion

SHEA Guidelines May 2003– Measures for the control of MRSA

• Gloves IA• Gowns IA• Active surveillance cultures to identify the

reservoir for spread IA• Periodic (eg. weekly) surveillance cultures are

indicated for patients remaining in the hospital at high risk for MRSA (IA)

IA- Strongly recommended for implementation and strongly supported by well-designed experimental, clinical, or epidemiologic studies.

But the question is…

What is the quality of the data and how is the body of current

studies best interpreted?

It is important to consider the limitations and challenges of

epidemiologic study methodology.

Epidemiology• The study of how disease is distributed in

populations and of the factors that influence or determine this distribution.– Determine risk factors for a given disease– Determine the extent of disease in a population– Study natural history of a specific disease– Evaluate existing and new preventive and

therapeutic measures – Provide the foundation for developing public policy

and regulatory decisions related to healthcare

Epidemiologic Approach• Define associations between exposure and an

outcome– Associations are not always causal!!!!!!!!

• Most data:– Descriptive

• Case control• Cohort

– Observational• Retrospective• Prospective (less common)

– Frequently non-randomized– Frequently not ‘controlled’– The ‘prospective, randomized clinical trial’ is a

rarity in epidemiology

Guidelines for Evaluating the Evidence of a Causal Relationship

• Temporal relationship• Biological plausability• Consistency

– Single studies are rarely definitive!• Alternative explanation

– Confounding assessed– single vs multiple simultaneous interventions

• Dose-response• Strength of association• Cessation effects

Leon Gordis. Epidemiology. 2nd Ed.W.B Saunders. 2000

So prospective, randomized trials are a rarity in epidemiology.

Additionally, there are 2 other phenomenon which make many hospital epidemiology studies problematic:

1.Multiple simultaneous interventions:Relative effect of each is impossible to define

2. Regression toward the mean :Introduction of bias and threat to validity

Regression Toward the Mean• What is it?

– Regression to the mean is a statistical phenomenon that is a fact of life in statistics.

– Variation:• The variations are usually due to the normal

randomness of occurrence that is present

Number of crashes at an intersection

over time

Number of crashes at an intersection

over time

Regression Toward the Mean

• The average does not change

NSICU Bloodstream InfectionsQuarterly Rates, 1998-2003

8.6

27.4

0.0

3.92.3

8.4

14.011.9

5.4

2.04.2 4.3 4.2

9.0

15.7

10.6

15.8

7.2

10.9

15.2

6.6

12.5

16.9

6.6

0

5

10

15

20

25

30

NNIS

Infections/1,000 catheter days

1998 1999 2000 2001 2002 2003

Regression to the mean is applicable to hospital epidemiology

Regression Toward the Mean

Conclusion: The intervention workedConclusion: The intervention worked

Intervention introduced at first arrow

Intervention introduced at first arrow

Effect of intervention measured at second arrow

Effect of intervention measured at second arrow

Kudos to you!!!!! This is a great study!!!…or is it really?Kudos to you!!!!! This is a great study!!!…or is it really?

Regression Toward the Mean• Why is it important?

– It is an important phenomenon to take note of in conducting experiments because it affects the internal validity of the experimental design.

– One can end up concluding that the significant difference or effect is due to the treatment when in fact it is due to chance and by this phenomenon known as regression toward the mean.

– Occurs in all experimental designs and especially in quasi-experiments where nonequivalent groups and non-random assignment are used.

Regression Toward the Mean• When interventions under investigation

are made because of unusually high MRSA levels, there is a risk that subsequent reduction in MRSA will be attributed solely to that intervention– Reporting bias is usually assumed to result

from authors’ and journals’ preferences for publishing positive results.

Cooper et al. Health Technology Assessment 2003; Vol. 7:No. 39S y s te m a tic re v ie w o f is o la tio n p o lic ie s in th e h o s p ita l m a n a g e m e n t o f m e th ic illin -re s is ta n t S ta p h y lo c o c c u s a u re u s : a re v ie w o f th e lite ra tu re w ith e p id e m io lo g ic a l a n d e c o n o m ic m o d e llin g

B S C oope r1 S P S tone 1* C C K ibb le r2 B D C ookson 3,4 JA R obe rts 4 G F M ed ley 5 G J D uckw o rth 6 R La i7 S Eb rah im 8

1

Cooper et al. Health Technology Assessment 2003; Vol. 7:No. 39Background

The incidence of patient infection and colonisation with methicillin-resistant Staphylococcus aureus (MRSA) continues to rise in UK hospitals

Poses a considerable socio-economic burden.

Management of this problem includes screening to detect asymptomatic carriers and the use of various isolation measures to control its spread.

There has been much debate about the rationale and cost-effectiveness of these measures.

MRSA guidelines have been published but there was an urgent need for a systematic review to examine the evidence base for these recommendations.

Cooper et al. Health Technology Assessment 2003; Vol. 7:No. 39

Objectives • To review the evidence for the effectiveness of

different isolation policies and screening practices

• To develop transmission models to study the

effectiveness and cost-effectiveness of isolation

policies in controlling MRSA.


Data sources

•Searches of electronic databases MEDLINE (1966–

2000), EMBASE (1980–2000), CINAHL (1982–

2000), The Cochrane Library (2000) and SIGLE

(1980–2000).

•Manual searches of the principal hospital infection

journals to validate electronic database

searches.

•No language restrictions were imposed.

Cooper et al. Health Technology Assessment 2003; Vol. 7:No. 39Study selection

•

Abstracts were appraised by two or three reviewers

•

Two investigators reviewed the full papers independently

•

Data Extracted where studies were

•

prospective

•

employed planned comparisons using retrospective data

•

isolation wards or nurse cohorting were used (designated

nurses for the care of MRSA-affected patients).


D a ta e x tra c tio n : •d e ta ils o f a ll p o p u la tio n s u n d e r in v e s tig a tio n

•d e ta ils o f p a tie n t is o la tio n , s c re e n in g a n d o th e r in fe c tio n

c o n tro l m e a s u re s (e .g . e ra d ic a tio n o f c a rr ia g e ,

a n tib io tic re s tr ic tio n , h a n d -h yg ie n e , fe e d b a c k , w a rd

c lo s u re s )

•in fo rm a tio n o n o u tc o m e s (e .g . in fe c tio n , c o lo n is a tio n ,

b a c te ra e m ia , d e a th )

•d e ta ils o f p o te n tia l c o n fo u n d e rs o r e ffe c t m o d ifie rs

in c lu d in g le n g th o f s ta y , a n tib io tic u s e , s tra in c h a n g e ,

p re -e x is tin g tre n d s , n u m b e rs c o lo n is e d o n a d m is s io n ,

s e a s o n a l e ffe c ts , s ta ffin g le v e ls a n d a s p e c ts o f s tu d y

d e s ig n th a t m ig h t in tro d u c e b ia s e s .


Data synthesis •Data were summarised in table form.

• Formal meta-analysis was considered inappropriate owing to

heterogeneity in study design and patient populations.

•The strength of evidence was assessed

• study design

• quality of data

• size of effect and presence of plausible alternative explanations due

to confounders and biases.


Study interventions •Eighteen studies described the use of isolation wards.

• Study durations ranged from 3 months to 15 years

• involved between 11 and 5345 MRSA cases.

•Nine studies described the use of nurse cohorting (NC).

• Study durations ranged from 3.5 months to 4 years

• involved between 5 and 1074 MRSA cases.

•Nineteen studies described other isolation policies.

• Study durations ranged from 1 month to 9 years,

• involved between 9 and 1771 cases.

•In nearly all the studies isolation was combined with at least

one other simultaneous intervention.


Results: systematic review

•

There were 4382 abstracts

•

254 full-article appraisals

•

Forty-six were included in

the final review.


S tu d y d e s ig n s •

o n e p ro s p e c tive c o h o rt c ro s s -o v e r s tu d y

• tw o p ro s p e c tive c o h o rt s tu d ie s w ith h is to r ic a l

c o n tro ls

• n in e p ro s p e c tive in te rru p te d tim e s e r ie s (IT S )

(th re e h a d p ro s p e c tiv e d a ta c o lle c tio n b u t

u n p la n n e d in te rv e n tio n s )

• s ix p ro s p e c tive o b s e rv a tio n a l o n e -p h a s e

s tu d ie s

• f iv e h y b rid re tro s p e c tiv e /p ro s p e c tive IT S

• o n e re tro s p e c tiv e c o h o rt s tu d y w ith s y s te m a tic

d a ta c o lle c tio n a n d th e c o m p a ris o n d e c id e d o n

in a d va n c e o f e x a m in in g th e d a ta

• tw o re tro s p e c tiv e s tu d ie s w ith th e c o m p a ris o n

d e c id e d o n b e fo re e x a m in a tio n o f th e d a ta

• e ig h te e n re tro s p e c tiv e IT S

• tw o re tro s p e c tiv e o b s e rv a tio n a l s tu d ie s .


Quality of studies •There were few formally planned prospective studies

with predefined pre- and postintervention periods.

•Systematic assessment and adjustment for potential

confounders was lacking.

•Regression to the mean effects and confounders were

plausible threats to the validity of many studies.

•The predominance of unplanned retrospective reports

suggests that reporting bias may be important.

•Statistical analysis was absent or inappropriate in all

but two studies.

•There was no robust economic evaluation.


Results •No conclusions could be drawn about the effect of isolation in one-third of studies.

•In studies with multiple simultaneous interventions it was not possible to assess the

relative contribution of individual measures.

•Most others provided evidence consistent with reduction of MRSA.

• In half of these, the evidence was considered weak because of poor design,

major confounders and/or risk of systematic biases.

•Two studies presented evidence consistent with immediate isolation reducing

transmission.


• Three presented conflicting evidence of the effectiveness of isolation : – one study reduced infection– one study did not reduce infection– one study resulted in control for many years until a change in

strain and/or an increase in the number of patients colonisedon admission overwhelmed the institution.

• One study presented evidence that single-room isolation with screening, eradication and an extensive hand-hygiene program reduced MRSA infection and colonisation hospital wide.

• One study provided evidence that NC in single rooms with screening and eradication reduced infection hospital wide.

• One pediatric intensive care unit study provided evidence that single-room isolation and patient cohorting in bays (with screening, feedback of infection rates and hand-hygiene education) reduced infection

6 Studies of note

Cooper et al. Health Technology Assessment 2003; Vol. 7:No. 39Conclusions

Implications for healthcare

• Intensive concerted interventions that include isolation can

substantially reduce MRSA

• Little evidence was found to suggest that current isolation measures

recommended in the UK are ineffective, and these should continue to

be applied until further research establishes otherwise.

• It was not possible to draw any conclusions about the cost-

effectiveness of the interventions because of the poor quality of the

economic evaluative work presented.

ICHE 2004. Vol 25. No.5 pgs 395-401

• Do Infection Control Measures Work for Methicillin-Resistant Staphylococcus aureus?

• John M. Boyce, MD; Nancy L. Havill, MT; Cynthia Kohan, MT, MS; Diane G.Dumigan, RN, BSN; Catherine E. Ligi, RN, BSN

ICHE 2004. Vol 25. No.5 pgs 395-401• Design

– To review evidence regarding the effectiveness of control measures in reducing transmission of methicillinresistant Staphylococcus aureus (MRSA) in hospitals.

• Setting– A 500-bed, university-affiliated, community

teaching hospital.

ICHE 2004. Vol 25. No.5 pgs 395-401• Results:

– The percentage of nosocomial S. aureusinfections caused by MRSA increased significantly between 1982 and 2002

– Ineffectiveness of control measures may be due to several factors including the failure to identify patients colonized with MRSA.

• Stool specimens submitted for Clostridium difficile toxin assays

– 12% of patients had MRSA in their stool» 41% of patients with unrecognized colonization were

cared for without using barrier precautions.• Poor adherence of healthcare workers (HCWs) to

recommended precautions• Transmitting MRSA, and importation of MRSA by

patients admitted from other facilities.

ICHE 2004. Vol 25. No.5 pgs 395-401• Evidence that implementing SHEA

guidelines for the control of MRSA is possible– Their intervention

• Staged approach to implementing and expanding MRSA surveillance cultures

– SICU» Cultures of anterior nares obtained on all SICU

admissions and then q 7 days» Contact precautions and individual patient

rooms? (not specified in text)

ICHE 2004. Vol 25. No.5 pgs 395-401• 5 months of intervention data

– 442 active surveillance cultures (84.5%) of patients admitted to SICU• 38 (8.6%) Pts had previous MRSA history

– 23 (5.2%) of 442 had positive MRSA surveillance culture

• 404 (94.4%) of those cultured had NO MRSA by history

– 24 (5.4%) of these had a positive surveillance culture. Unrecognized COLONIZATION

– Only 4 (0.9%) of 404 with negative screening cultures ultimately had a positive MRSA culture on surveillance

ICHE 2004. Vol 25. No.5 pgs 395-401• Impact of their intervention:

– 6 month study period prior to intervention• Proportion of patients in SICU with MRSA associated

nosocomial infection- 2.2%• 0.48 MRSA infections per 100 patient days

– After 5 months of intervention• Proportion of patients in SICU with MRSA associated

nosocomial infection- 0.7% (P=0.033)• 0.22 MRSA infections per 100 patient days

– NO P Value or TEST OF SIGNIFICANCE CITED

ICHE 2004. Vol 25. No.5 pgs 395-401• The authors’ conclude:

– ‘MRSA control programs are effective if they include ASCs of high-risk patients, use of barrier precautions when caring for colonized or infected patients, hand hygiene, and treatingHCWs implicated in MRSA transmission’

• HOWEVER:– Study design

• Intervention of limited time frame (5 months)– No data on patient acuity in pre/post intervention– No data on device specific/nosocomial infection type– No data on compliance with hand hygiene and

contact precaution• Regression to the mean is a significant threat to validity• No economic or cost benefit analysis; instead authors

cite prior studies to justify the expense

The bottom line:• SHEA guidelines suggest that current MRSA

isolation practices are supported by incontrovertible evidence.– However, a critical review of the literature

suggests that much of the supporting data is limited by flaws of study design, confounding and analysis.

• The quality of the data in many studies is weak– There is no significant evidence that current MRSA

control practice is ineffective.– The cost effectiveness of MRSA control practices is

still largely inconclusive

What may be some of the unintended consequences of contact precautions?

JAMA. 2003;290:1899-1905.

Safety of Patients Isolated for Infection Control

Henry Thomas Stelfox, MD; David W. Bates, MD, MSc; Donald A.Redelmeier, MD, MSc

JAMA. 2003;290:1899-1905.• Context

– Hospital infection control policies that use patient isolation preventnosocomial transmission of infectious diseases, but may inadvertently lead to patient neglect and errors.

• Objective– To examine the quality of medical care received by patients isolated

for infection control.• Design, Setting, and Patients• Adults isolated with MRSA at 2 academic centers

– General cohort (patients admitted with all diagnoses between January 1, 1999, and January 1, 2000; n = 78)

– Disease-specific cohort (patients admitted with a diagnosis of congestive heart failure between January 1, 1999, and July 1, 2002; n = 72).

– Two matched controls were selected for each isolated patient (n = 156 general cohort controls and n = 144 disease-specific cohort controls).

JAMA. 2003;290:1899-1905.

• Main Outcome Measures– Quality-of-care measures

• encompassing processes• outcomes• patient satisfaction

– Adjustments for study cohort and patient demographic, hospital, and clinical characteristics were conducted using multivariable regression.

Safety of Patients Isolated for Infection Control: Process Measures

<.0012.912%7%24%43%Days w/ no MD progress note

<.0011.779%17%11%11%Days w/ no nursing notes

.022.551%5%1%6%Days w/ no VS recorded

<.0011.9210%19%8%10%VS incomplete

PTest

statisticControlsN-144

IsolatedN-72

ControlsN-156

IsolatedN-78

Isolated vs controlsCHF CohortGeneral Cohort

Stelfox HT et al. JAMA 2003;290:1899-1905.

Safety of Patients Isolated for Infection Control: Outcome Measures

<.00123.55%17%5%38%Patient complaint

<.0018.271.8%16.2%0.8%6.1%Supportive care failure*

<.0012.2024.547.37.017.0Adverse events/1000 days

PRRControlsIsolatedControlsIsolated

Isolated vs controlsCHF CohortGeneral Cohort

*falls, pressure ulcers, fluid/electrolyte disorders

Stelfox HT et al. JAMA 2003;290:1899-1905.

JAMA. 2003;290:1899-1905.

• Conclusion• Compared with controls, patients

isolated for infection control precautions:–Experience more preventable adverse

events– express greater dissatisfaction with

their treatment–have less documented care.

Conclusion• There is reason to debate aggressive MRSA

control policies as advocated by SHEA• A critical review of the literature suggests

that the quality of the supporting data, as referenced by SHEA, does not allow for a conclusive and definitive position on MRSA control.

• There may be unintended consequences of infection control contact isolation and these may pose a threat to patient safety and healthcare quality.

• …..the debate continues

Documents

Control of Endemic MRSA Current Evidence and Controversies